We shall characterize the glycolipid alterations which occur in brain as a result of slow virus infections. Brain tissue will be obtained from animals infected with Kuru, Creutzfeldt-Jacob (C-J) disease, scrapie and mink encephalopathy, and from human victims of such diseases as C-J and SSPE. Initially we shall examine gray matter, white matter and plaque areas for gross changes in ganglioside and neutral glycosphingolipid composition, but the major effort will be devoted to analysis of these substances in individual cell types. Methods are now available for isolating bulk quantities of neurons, astrocytes and oligodendroglia from fresh tissue and neurons from frozen brain. Certain subcellular fractions will also be examined, principally synaptosomes and myelin. By using individual cell types and fractions we hope to differentiate specific changes induced by the various slow viruses from more diffuse alterations due to altered cell populations within the tissue. Brain from multiple sclerosis patients will also be subjected to quantitative glycolipid analysis in an effort to detect possible parallels with the slow virus diseases. Our recent discovery that ganglioside G7 (sialosylgalactosylceramide) is present in normal human white matter but completely absent from MC plaques will be followed up by studying the cellular origin of G7 and its relation to the MS lesion. The spinal fluid concentration of gangliosides will be measured in MS patients and also the subhuman primates with kuru and C-J disease to determine whether the ganglioside changes already observed in brain tissue are reflected here.